Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats.
Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats.
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姜黄素可减轻实验性糖尿病大鼠的糖尿病心肌病。
DOI：
10.1371/journal.pone.0052013
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Yu W;Wu J;Cai F;Xiang J;Zha W;Fan D;Guo S;Ming Z;Liu C
糖尿病心肌病（DCM）以心肌结构和功能改变为特征，是糖尿病个体中发生的一种独立的心肌病。本研究旨在探讨姜黄素对 DCM 调节的作用及其机制。采用低剂量链脲佐菌素(STZ)联合高能量摄入诱导大鼠实验性糖尿病模型。姜黄素口服剂量分别为100或200 mg·kg−1·d−1。通过连续超声心动图评估心脏功能。通过组织病理学分析评估心肌超微结构、纤维化面积和细胞凋亡。通过生化测试检查代谢特征、心肌酶和氧化应激。通过ELISA检测炎症因子，并通过蛋白质印迹测量相关蛋白。 DCM大鼠心肌收缩功能下降，心肌肥厚、纤维化，伴有代谢异常、心肌酶谱异常、AGEs（晚期糖基化终末产物）积累和RAGE（AGEs受体）表达增加、氧化应激标志物（MDA、SOD、NADP+/NADPH比值、Rac1活性、gp91phox和NADPH氧化酶亚基表达升高） p47phox ），升高炎症因子（TNF-α 和 IL-1β），增强凋亡细胞死亡（bax/bcl-2 比率、caspase-3 活性和 TUNEL），减少 Akt 和 GSK-3β 磷酸化。值得注意的是，姜黄素可以减轻糖尿病大鼠心脏的心肌功能障碍、心脏纤维化、AGEs 积累、氧化应激、炎症和细胞凋亡。姜黄素处理也可以恢复 Akt 和 GSK-3β 磷酸化的抑制。总而言之，这些结果表明姜黄素通过减轻纤维化、氧化应激、炎症和细胞死亡，在扩张型心肌病（DCM）以及其他心血管疾病的治疗中可能具有巨大的治疗潜力。此外，Akt/GSK-3β 信号通路可能参与介导这些作用。
Diabetic cardiomyopathy (DCM), characterized by myocardial structural and functional changes, is an independent cardiomyopathy that develops in diabetic individuals. The present study was sought to investigate the effect of curcumin on modulating DCM and the mechanisms involved. An experimental diabetic rat model was induced by low dose of streptozoticin(STZ) combined with high energy intake on rats. Curcumin was orally administrated at a dose of 100 or 200 mg·kg−1·d−1, respectively. Cardiac function was evaluated by serial echocardiography. Myocardial ultrastructure, fibrosis area and apoptosis were assessed by histopathologic analyses. Metabolic profiles, myocardial enzymes and oxidative stress were examined by biochemical tests. Inflammatory factors were detected by ELISA, and interrelated proteins were measured by western blot. Rats with DCM showed declined systolic myocardial performance associated with myocardial hypertrophy and fibrosis, which were accompanied with metabolism abnormalities, aberrant myocardial enzymes, increased AGEs (advanced glycation end products) accumulation and RAGE (receptor for AGEs) expression, elevated markers of oxidative stress (MDA, SOD, the ratio of NADP+/NADPH, Rac1 activity, NADPH oxidase subunits expression of gp91phox and p47phox ), raised inflammatory factor (TNF-α and IL-1β), enhanced apoptotic cell death (ratio of bax/bcl-2, caspase-3 activity and TUNEL), diminished Akt and GSK-3β phosphorylation. Remarkably, curcumin attenuated myocardial dysfunction, cardiac fibrosis, AGEs accumulation, oxidative stress, inflammation and apoptosis in the heart of diabetic rats. The inhibited phosphorylation of Akt and GSK-3β was also restored by curcumin treatment. Taken together, these results suggest that curcumin may have great therapeutic potential in the treatment of DCM, and perhaps other cardiovascular disorders, by attenuating fibrosis, oxidative stress, inflammation and cell death. Furthermore, Akt/GSK-3β signaling pathway may be involved in mediating these effects.